Attempts to abrogate the harmful effects of abnormal expression of growth factors or infection by microbes can be made at the site of production or at its target. Our efforts have been directed towards the latter. By representing receptor molecules as an array of overlapping peptide segments and measuring the binding of intact ligand we have found four potential targets within the receptor for Interleukin-6 which bind human IL-6. Within HIV-1 co-receptor sequences we found four in CD4, six in CCR5, four in CXCR4 and nine in STRL33 which bind HIV envelope protein gp120. Authenticity of the of the IL-6 binding was provided by neutralization with IL-6 antiserum and correlation with bioassay for IL-6. Authenticity of the HIV-1 gp120 binding was provided by correlation with virus attachment and entry. Thus, in these cases simple binding was predictive for more complex biological systems as well as showing potential savings of time and effort of nearly an order of magnitude when assisted by automated synthetic peptide array synthesis. Since the binding patterns of gp120 showed a lesser degree of biological host-related restriction than HIV, it follows that additional structural information, post-binding steps and/or reactants are required to engender host specificity. This is turn suggests ways to circumvent the HIV genetic evolution problem. Even more importantly, the process, which has been proven in concept by these results, is extremely versatile and may in principle be applied to any set of interacting molecules. Clearly, the identification of receptor peptides which bind the ligand leads directly to potential inhibitors of the receptor-ligand interaction. Identification of the ligand site(s) interacting with active receptor peptides can, in turn, be observed by homologous displacement with peptides derived from the ligand structure or antisera against specific ligand sites and provides leads to potential vaccine targets. Furthermore, this knowledge provides leads to increasing our knowledge of fundamental receptor mechanisms. - AIDS, chemokine receptors, Cytokine Receptors, binding protein, HIV, molecular interactions, molecular evolution, peptides, therapeutics, vaccine design, receptors,